Transcatheter aortic valve implantation (TAVI) is predominantly utilized for patients diagnosed with aortic stenosis (AS). However, with the ongoing advancements in valve technology and stent design, a growing cohort of patients with pure aortic regurgitation (PAR) are receiving TAVI [1]. A common complication associated with TAVI is the need for permanent pacemaker implantation (PPI). The incidence of PPI following atrioventricular block in AS patients undergoing TAVI varies between 3.4% and 25.9% [2]. In contrast to AS, PAR, characterized by regurgitated flow due to aortic valve leaflet dysfunction, leads to left ventricular dilation and volume overload, presenting unique challenges compared to the calcific stenosis in AS. This distinction may impact TAVI procedures and the need for PPI, with PAR patients showing a higher PPI requirement post-TAVI, likely due to the altered left ventricular outflow tract geometry and increased risk of conduction disturbances [3].

Although prior research has indicated that pacemaker implantation, particularly with leads positioned in the right ventricular apex, is associated with an increased risk of heart failure and atrial fibrillation [4, 5], the impact of PPI on cardiac function following TAVI in AS patients remains a subject of debate [6]. A growing body of clinical trials suggests that PPI may increase hospitalization rates and mortality among these individuals [7, 8]. Consequently, this study is designed to investigate the effects of PPI on PAR patients during a six-month follow-up period after TAVI, addressing a gap in the literature where the influence of PPI on cardiac function and prognosis in PAR patients post-TAVI has yet to be documented.

By bridging this knowledge gap, this research will provide valuable insights into the effects of PPI on cardiac function and prognosis, which will be instrumental in refining patient selection, procedural strategies, and post-procedure management. Ultimately, these findings will contribute to the development of guidelines for the management of PAR patients undergoing TAVI, with a particular focus on the decision-making process for PPI.

This study represents the first investigation into the effects of PPI on short-term mortality, adverse events, and cardiac function in PAR patients following TAVI. The findings indicate that PPI is not associated with mortality or the incidence of adverse events after six months among PAR patients. Factors such as advanced age, elevated creatinine levels, and prior cerebral embolism were identified as contributors to increased mortality post-TAVI.

Regarding the impact of PPI on cardiac structure and function post-TAVI, the PACE-TAVI registry revealed that AS patients with a right ventricular pacing (RVP) ratio of 40% exhibited improved cardiac function post-TAVI compared to preoperative levels; however, those with an RVP ratio $>$40% experienced diminished cardiac function and a higher rate of heart failure-related rehospitalization [7]. A recent meta-analysis indicated that RVP is associated with a 2.9% reduction in LVEF, alongside reductions in left ventricular stroke volume and increases in both left ventricular end-diastolic and end-systolic diameters [17, 18]. This is consistent with previous literature, which states that long-term right ventricular pacing has been associated with right ventricular desynchronization, negative left ventricular remodeling, and heart failure. In contrast, physiological pacing methods, such as His-bundle pacing and left bundle branch area pacing (LBBaP), have emerged as novel physiological pacing modalities, showing excellent results for patients with conventional indications for bradycardia pacing [19]. In Wang et al.’s study [20], patients who underwent TAVI and received either RVP or LBBaP exhibited a significant reduction in LVEDD over a five-year follow-up period, irrespective of their baseline LVEF being below 50%. Additionally, both groups demonstrated a notable enhancement in LVEF, with the LBBaP group showing a more marked improvement [20]. This study demonstrated that among AR patients post-TAVI, regardless of PPI, a trend towards decreased left ventricular size and increased LVEF was observed. Notably, significant alterations in left ventricular dimensions and LVEF may manifest with extended follow-up.

The relationship between PPI and mortality or rehospitalization rates post-TAVI remains contentious. Numerous studies have established that PPI correlates with increased rehospitalization and mortality rates among patients undergoing TAVI [21, 22]. The PACE-TAVI registry also indicated that patients with an RVP ratio $>$40% faced heightened cardiovascular mortality and heart failure rehospitalization rates [7]. A four-year follow-up study confirmed that PPI can elevate heart failure hospitalization rates and adversely affect cardiac function recovery, particularly in patients with prior LVEF 50% [8]. In patients with LVEF $\le$40%, CRT was associated with improved survival compared to non-CRT [23]. For TAVI patients with preserved LVEF, postoperative left ventricular desynchronization due to high-burden RVP or permanent left bundle branch block was linked to a significantly increased risk of death and cardiomyopathy at one-year follow-up [24, 25]. A five-year follow-up after TAVI revealed that patients with RVP had a significantly higher risk of readmission compared to those with LBBaP (21.4% vs. 7.5%; 95% CI: 1.01 to 5.08; p = 0.048) [20]. However, Mohananey et al. [26] analyzed outcomes in patients with PPI and without PPI after TAVI at 30-day and one-year follow-ups, finding no significant differences in all-cause mortality, cardiovascular mortality, or myocardial events between the groups. In this study, PPI were not associated with rehospitalization or mortality, possible reasons include the short follow-up period of this study, where the short-term impact of PPI on cardiac function may not be significant, but long-term effects could lead to increased hospitalization for heart failure and mortality; the small sample size and lack of stratification based on patients’ ejection fraction (EF) values may also have influenced the results of this experiment, necessitating further research to elucidate the prognostic implications of varying LVEF levels among PAR patients undergoing TAVI.

The debate surrounding whether PPI increases mortality post-TAVI persists, yet other factors contributing to elevated mortality rates have been identified. Advanced age and myocardial fibrosis have been shown to increase mortality rates among AS patients post-TAVI [27]. In a cohort of 500 patients undergoing TAVR, with a median follow-up of 5.2 years, advanced age, male gender, chronic kidney disease stage $\ge$3, diabetes mellitus, and coronary heart disease were associated with heightened mortality risk, while coronary artery bypass grafting did not mitigate this risk [28]. Interestingly, hypertension did not significantly impact mortality [26]. Post-TAVI bleeding, particularly major or life-threatening bleeding, was found to elevate the 30-day postoperative mortality of rates [29]. A large meta-analysis by Eggebrecht et al. [30] reported that the 30-day mortality rate following a stroke was 3.5 times higher. The one-month mortality rate reached 25% among patients with cerebral embolism, compared to 7% for those without [31]. This study corroborated that advanced age and cerebral infarction increased mortality rates post-TAVI, while hypertension unexpectedly emerged as a protective factor, potentially due to systemic hypotension leading to cerebral hypo perfusion, thereby increasing mortality risk [31].

The small sample size and the short follow-up period constrain the generalizability of our findings and limit our capacity to assess the long-term outcomes effectively. Future research endeavors should aim to incorporate larger cohorts and extended follow-up periods to more accurately determine the effects of PPI on survival and cardiac function in PAR patients post-TAVI. Furthermore, the absence of LVEF stratification in our analysis represents a significant limitation, suggesting a clear need for future studies to explore the nuanced impact of PPI across different LVEF levels. Such larger, longitudinal studies are essential to establish the definitive role of PPI in the management of PAR patients following TAVI, ultimately informing clinical practice and patient care standards.

Our study, the first to examine the short-term impact of PPI on patients with PAR following TAVI, reveals no association between PPI and increased mortality or adverse events within the initial six-month follow-up. Notably, advanced age, elevated creatinine levels, and a history of cerebral infarction emerged as significant predictors of mortality, thereby underscoring their critical role in post-TAVI care. Overall, these findings provide valuable insights into the management strategies for PAR patients in the aftermath of TAVI, highlighting the need for tailored approaches based on individual patient characteristics.

AS, aortic stenosis; CRT, cardiac resynchronization therapy; LBBaP, left bundle branch area pacing; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; PAR, pure aortic regurgitation; PPI, permanent pacemaker implantation; RVP, right ventricular pacing; TAVI, transcatheter aortic valve implantation.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

CJ designed the research, collected data and wrote the manuscript. YZ completed the data analysis, SC and ZG designed the research and revised the manuscript. TG and ST performed the research. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. All procedures involving human participants were approved by the Scientific Research and New Technology of Wannan Medical College Yijishan Hospital’s Ethics Committee (Grant No. [2024]23), and informed consent was obtained from all participants.

We would like to express their gratitude to EditSprings (https://www.editsprings.cn/) for the expert linguistic services provided.

This study was supported by the Key Specialty Project of Anhui Province Medical and Health (Award Number: KZSJZ008), Anhui Province Quality Engineering Research Project (Award Number: 2023jyxm1238) and Enterprise-commissioned R&D projects (Award Number: KY21610724).

The authors declare no conflict of interest.